Appendix

References

Ref 1; Eurosciences Communication 2000

Ref 2; see below;

Medical Evidence for the Benefit of the Mediterranean Diet and its Constituents including Olive Oil.

Thousands of scientific studies now provide an overwhelming evidence base to support the health benefits of the Mediterranean Diet. It is not possible to usefully list all of the references in this appendix.

There is also a body of published data that defines the role of individual components of the diet, including olive oil, nuts, vegetable and fruits etc.

Examples of excerpts from medical and scientific journals below include review articles which draw conclusions from numerous published studies. In addition the evidence is cited in documents produced by organisations such as The American Heart Association, the National Standards Framework for Cardiovascular Disease and in numerous National Health Service documents.

The following excerpts from medical and scientific journals reveal the depth and breadth of the evidence for the "Gold Standard" status of traditional Mediterranean eating patterns.

The Mediterranean Diet has been associated with lower risk for several forms of cancer, obesity, dyslipidemia, hypertension, abnormal glucose metabolism, coronary heart disease, and overall mortality. In a recent study, we demonstrated that higher adherence to the Mediterranean Diet at baseline evaluation was associated with lower risk of developing Alzheimer�s disease during follow-up. Similarly to our previous findings, in this different Alzheimer's disease population we observe that higher adherence to the Mediterranean Diet is associated with reduced disease odds. Similarly to our previous report, we note a gradual reduction in Alzheimer's disease risk for higher tertiles of Mediterranean Diet adherence, suggesting a possible dose-response effect. Additionally, in accordance with our previous results, the associations between Mediterranean Diet and Alzheimer�s disease remain unchanged and significant even when simultaneously adjusting for the most commonly considered potential confounders for Alzheimer�s disease, such as age, sex, ethnicity, education, APOE genotype, caloric intake, and BMI. Higher adherence to Mediterranean Diet reduced risk for probable Alzheimer�s disease either with or without coexisting stroke.

A systematic review was made and a total of 43 articles corresponding to 35 different experimental studies were selected. Results were analyzed for the effects of the Mediterranean diet on lipoproteins, endothelial resistance, diabetes and antioxidative capacity, cardiovascular diseases, arthritis, cancer, body composition, and psychological function. The Mediterranean diet showed favorable effects on lipoprotein levels, endothelium vasodilatation, insulin resistance, metabolic syndrome, antioxidant capacity, myocardial and cardiovascular mortality, and cancer incidence in obese patients and in those with previous myocardial infarction.

The findings support the hypothesis that a Mediterranean diet that emphasizes olive oil, fiber, fruits, vegetables, fish, and alcohol and reduces meat and meat products can be an effective measure for reducing the risk of coronary heart disease. The benefits of the Mediterranean diet were significant in all studies. The reduction in the risk of coronary heart disease varied from study to study, but this also reflects the different increments used, explicitly or implicitly, in these studies. To our knowledge there are no studies that have shown a detrimental or non-significant impact of the Mediterranean diet on cardiovascular disease.

The main finding of this study is that high adherence to the traditional Mediterranean dietary pattern, characterized by high intakes of vegetables, fruits, legumes, fish, cereals, and nuts and low and moderate consumption of meat and wine, respectively, is associated with a lower prevalence of obesity in men and women in this Mediterranean population. This association held even after controlling for age, leisure time physical activity, educational level, smoking, and alcohol consumption.

Recent findings showing that elderly African Americans and Japanese living in the USA have a much higher prevalence of AD (6.24% and 4.1%, respectively) than those still living in their ethnic homelands (< 2%) suggest that the prevalence of Alzheimer�s disease is more strongly influenced by diet and nutrition, environment and/or lifestyle than by genetics� In conclusion, the Mediterranean diet pattern based on complex carbohydrates, fibre and non-animal fat appears to protect against age-related cognitive decline and cognitive decline of vascular or degenerative origin.

The present study provides a pathophysiologic explanation to the growing scientific evidence for the beneficial effect of the Mediterranean diet on human health and, especially, atherosclerotic disease. We found that greater adherence to this traditional diet was independently associated with a reduction in the inflammation and coagulation indexes that are believed to have an important role in CVD. The World Health Organization reports that the three major components involved in preventing atherosclerotic disease are smoking, physical inactivity, and an unhealthy diet, as they are factors that can be changed. Our findings emphasize the need for actions from public health care professionals in order to prevent the development and progression of atherosclerotic diseases through the adoption of low animal fat diets, like the Mediterranean diet.

Adherence to the Mediterranean diet attenuates inflammation and coagulation process in healthy adults: the Attica studyChrysohoou, C., Panagiotakos, D.B., et al. Journal of the American College of Cardiology 44:152-158 (2004).

Greater adherence to the Mediterranean diet is associated with a significant reduction in total mortality. A one unit increase in a diet score, devised a priori on the basis of eight key features of the traditional common diet in the Mediterranean region, was associated with a 17% reduction in overall mortality.

Adherence to a Mediterranean diet and Survival in a Greek PopulationTrichopoulou A. et al The New England Journal of Medicine, 348:2599-2608 (2003).

Dietary intervention with the Mediterranean diet and statin treatment improve flow-mediated vasodilatation in the brachial artery in patients with ischemic heart disease and hyper-cholesterolemia to a greater degree than statin treatment alone.

The results indicate that patients with Rheumatoid arthritis, by adjusting to a Mediterranean diet, did obtain a reduction in inflammatory activity, an increase in physical function, and improved vitality.

Myocardial infarction patients can respond positively to simple dietary advice, and this can be expected to lead to a substantial reduction in the risk of early death. Regardless of any drug treatment prescribed, clinicians should routinely advise patients with myocardial infarction to increase their frequency of consumption of Mediterranean foods.

Efforts to combat nutrient deficiencies have centered on supplemental nutrient administration and addition of selected nutrients to the food chain in the form of food fortification. In addition to supplementation or forti-fication with specific nutrients, the consumption of certain dietary patterns (such as the Mediterranean diet) is associated with a reduced risk of chronic diseases, particularly cardiovascular diseases.�

Trichopoulou et al. report the results of a population-based study involved 22,043 apparently healthy adults in Greece, in which adherence to a traditional Mediterranean diet was associated with significantly lower total mortality, mortality from coronary heart disease, and mortality from cancer. To measure adherence to this diet, a score was constructed that incorporated relatively high intakes of vegetables, fruits and nuts, legumes, cereals, fish, and monounsaturated fat; relatively low intakes of meat, including poultry, and moderate consumption of alcohol. One intriguing aspect of this study is that despite a robust inverse association between the overall Mediterranean-diet score and mortality, no appreciable associations were seen for most of the individual dietary components used to construct the score. One possible explanation is that the effects of single nutrients of foods may be too small to detect, whereas the cumulative effective of multiple dietary components may be substantial. In addition, there may be synergistic or interactive effects among nutrients or foods, which the score automatically takes into account.

Until the picture can be clarified, lipid modification with strategies proved to reduce the risk for coronary events, such as statins or dietary changes in the style of the Mediterranean diet, should be better implemented in clinical practice.

Antioxidants, statins, and atherosclerosisGotto, AM. Journal of American College of Cardiology 41:1205-10 (2003).

In the Lyon Heart Study, higher ALA consumption in the context of a Mediterranean diet dramatically reduced total and cardiovascular mortality as well as nonfatal MI. These trials strongly support the protective effects of omega-3 fatty acids, including both ALA and fish oil, in secondary prevention of CHD. Mediterranean diet enriched with ALA reduced death by more than 70%.

The traditional Mediterranean diet as outlined in this article is an ideal eating pattern for prevention of cardiovascular disease. We believe that current understanding and scientific evidence are adequate to recommend this diet widely as a practical, effective, and enjoyable strategy � the new �gold standard� � in heart disease prevention.

The Indo-Mediterranean diet is a safe and economical way to improve the health of a non-Western population over 2 years. A diet enriched with fruit, vegetables, nuts, whole grains, and mustard or soy bean oil is associated with a pronounced decline in CAD morbidity and mortality, without an increase in non-cardiac deaths, and in the presence of improved metabolic profiles. The long-term benefits may be even more substantial.

Our data support the hypothesis that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. However, our results support the exclusion of refined cereals with a high glycaemic load as healthy elements of this pattern.

Mediterranean diet and reduction in the risk of a first acute myocardial infarction: an operational healthy dietary scoreMartinez-Gonzalez, M.A., Fernandez-Jarne, E., et al. European Journal of Nutrition 41(4): 153-160 (2002).

Based on the estimated risk model we found that the Mediterranean type of diet reduces significantly the risk of developing acute coronary syndromes even in the presence of unfavorable lifestyle situations, such as sedentary life, smoking habit, as well as hypertension, hyper-cholesterolemia and diabetes mellitus.

The role of traditional Mediterranean type of diet and lifestyle in the development of acute coronary syndromes: preliminary results from CARDIO 2000 studyPanagiotakis, D.B., Pitsavos, Ch., et al. Central European Journal of Public Health. 10(1-2): 11-5 (2002).

Long-term success in weight loss with dietary treatment has been elusive. A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.�

It would be short-sighted not to recognize the enormous public health benefit that the Mediterranean-style diet could confer� there is a pressing need to identify unknown risk Mediterranean diet itself on CHD. Other characteristics of factors and effective intervention strategies� The findings from the Lyon Diet Heart Study illustrate the importance of a [Mediterranean] dietary pattern that emphasizes fruits, vegetables, breads and cereals, and fish, within the context if a Step I diet� to dramatically lower CVD risk in the population and can be followed by free living people.

A Mediterranean-style diet demonstrates impressive effects on cardiovascular disease. Early reports from the Lyon Heart Study caused us to commission this advisory and to examine the current scientific basis for the effect of such dietary modifications in general; this led to recommendations for the AHA, practitioners, and the public. Because of the potentially substantial significance of their findings, we believe an aggressive pursuit of the issues raised in the study and the advisory must be undertaken. It does seem that substantial enhancement to the effectiveness of our current dietary recommendations may be provided by integrating the features of the diet used in the Lyon Diet Heart Study with current AHA guidelines. Studies addressing the issues listed in the scientific advisory will need to be completed before this conclusion can be drawn. Such studies should be aggressively pursued because of their major potential and societal impact.

The DART and the Mediterranean diet trials did show significant reduction in coronary heart disease in comparison with the placebo.

What Role for Statins: A Review and Economic Model [Treatment and Prevention]Updated 31-05-2001 NHS Centre for Reviews and Dissemination, University of York, U.K. (2001)

The most effective means of reducing the risk of sudden cardiac death (apart from the prophylactic implantation of a defibrillator) appears to be dietary prevention in the light of animal experiments, epidemiological studies and four randomized trials� Adoption of a dietary pattern, for instance a Mediterranean type of diet, seems to be the best way.

There is increasing scientific evidence of positive health effects from diets which are high in fruits, vegetables, legumes, and whole grains, and which include fish, nuts and low-fat dairy products. Such diets need not be restricted in total fat as long as there is not an excess of calories, and emphasize predominantly vegetable oils that are low in saturated fats and free of partially hydrogenated oils. The traditional Mediterranean Diet, whose principal source of fat is olive oil, encompasses these dietary characteristics.

The Mediterranean diet is a centuries-old tradition that contributes to excellent health, provides a sense of pleasure and well-being, and forms a vital part of the world�s collective cultural heritage. For Mediterranean peoples, this way of eating describes a traditional diet that can be readily preserved and revitalized within a modern lifestyle. For Americans, Northern and Eastern Europeans, and other who wish to improve their diets, the Mediterranean way of eating describes a dietary pattern that is attractive for its famous palatability as well as for its health benefits, and one that can be adopted in its entirety or adapted to a Mediterranean-style diet.

From the Scientific Exchange of the 2000 International Conference on the Mediterranean Diet

Adherence to the principles of the traditional Mediterranean diet� is likely to be associated with lower overall mortality. Moreover, key features of this diet appear to be transplantable to other dietary cultures and cuisines, and may have a substantial beneficial impact on the general mortality of elderly people who have the Westernized dietary habits. We conclude that a diet that adheres to thee principles of the traditional Mediterranean diet is associated with longer survival.

Are the Advantages of the Mediterranean Diet Transferable to Other Populations? A Cohort Study in Melbourne, AustraliaKouris-Blazos, A. British Journal of Nutrition 82: 57-61 (1999).

Adoption of a Mediterranean diet results in a significant reduction of total and LDL-cholesterol with also a significant effect on triglycerides and a small positive or no effect on HDL-cholesterol. However, the Mediterranean diet has been shown to be cardioprotective (for instance, prevention of sudden death) through biological effects (probably induced by omega-3 fatty acids) independent of its effect on blood lipoproteins. The association of these cardioprotective and beneficial effects on blood lipids, in addition to gastronomic properties, renders this type of diet extremely attractive for public health purposes.

There is increasing scientific evidence that there are positive health effects from [Mediterranean-type] diets which are high in fruits, vegetables, legumes, and whole grains, and which include fish, nuts, and low-fat dairy products. Such diets need not be restricted in total fat as long as there is not an excess of calories, and the diet is low in saturated fats and partially hydrogenated oils. Diets that emphasize vegetable oils (predominantly monounsaturated), nuts, and fish are preferable to those high in animal products and partially hydrogenated oils. Many individuals will have to limit their intake of fat or carbohydrate to avoid excess calories.

1998 Consensus Statement on Total Dietary Fat and the Overall Dietary PatternAmerican Journal of Medicine, January 30, 2003 Supplement (in press)From the Scientific Exchange of the 1998 International Conference on the Mediterranean Diet

Patients who followed a Mediterranean-type diet had reduced� combined all-cause mortality, nonfatal cancer, and myocardial infarction compared with those who followed an approximate American Heart Association Step 1 diet. The Mediterranean-type diet also showed a trend toward a decreased risk for cancer. A Mediterranean-type diet reduced mortality in patients with a first MI.

As conceptualized in the �Mediterranean� and �Asian-vegetarian� types of diet, it is very important that a healthy diet should be thought of as a whole rather than as a recitation of good and bad components. Although these protective dietary modifications should probably all be used in each patient to obtain maximal efficacy, these scientifically quantitated principles should be adapted to the culture, ethnic origin and �image of the world� of each patient in order to create an environment favourable to the perception of positive associations between various foods and healthy habits.

The Mediterranean diet was found not only to produce favorable effects on blood lipid profiles, but also to protect against oxidative stress and carcinogenesis� the dietary profile has maintained its basic features, and vital statistics still demonstrate a comparative advantage of eating behaviors in Mediterranean countries.

We present a food pyramid that reflects Mediterranean dietary traditions, which historically have been associated with good health. This Mediterranean diet pyramid is based on food patterns�. where adult life expectancy was among the highest in the world and rates of coronary heart disease, certain cancers, and other diet-related chronic diseases were among the lowest. The pyramid describes a dietary pattern that is attractive for its famous palatability as well as for its health benefits.

A Mediterranean diet with more cereal, vegetables, fruit, less saturated fats and more n-3 fatty acids has recently been shown to afford a rapid and exceptional protection from recurrences and death in coronary patients.

�Following Myocardial Infarction between 9 and 19 people will need to be given Mediterranean dietary advice to prevent 1 death - NHS Centre for reviews and dissemination�. Source British Dietetics Association

12th Congress of the European Society of Cardiology ��antioxidant effects of olive oil based on a number of bioactive substances�.�

�The wide range of antiatherogenic effects associated with olive oil consumption could contribute to explain the low rate of cardiovascular mortality found in Southern European countries in comparison with other Western countries, despite a high prevalence of CVD factors�

�Olive oil is the principle source of fat in the Mediterranean Diet which is associated with low mortality for cardiovascular disease�a large body of knowledge exists providing evidence of the benefits of olive oil consumption on secondary end points for cardiovascular disease. The benefits of olive oil consumption are beyond a mere reduction of the low density lipoprotein cholesterol�.

Pharmacol Research 2007 March; 55 175-86

The Mediterranean Diet, rich in olive oil, improves the major risk factors for cardiovascular disease�some of these effects are attributed to components of virgin olive oil.

International conference on the healthy effects of virgin olive oil. European Journal clinical Investigation 2005 July 35 421-4

�Olives and olive oil contain antioxidants in abundance..and substantial amounts of other compounds that are deemed to be anticancer agents�

The role of dietary extra virgin olive oil in preventing the onset of atherosclerosis and inflammatory bowel disease.

A report to the 12th international symposium on atherosclerosis Stockholm, Sweden. June 25-29. Masella et al, Rome.

�Antioxidant polyphenolic compounds such as quercetin- which is abundant in olive oil- help switch off the mechanisms which lead to atherosclerosis by inhibition of endothelial activation, the process by which the lining of the blood vessels contribute to the development of atherosclerosis�.Report to the 12th Congress of the European society of cardiology ,Amsterdam, 2000 . Carluccio, University Milan.

�Olive oil contains a vast range of substances such as monounsaturated free fatty acids (e.g., oleic acid), hydrocarbon squalene, tocopherols, aroma components, and phenolic compounds. Higher consumption of olive oil is considered the hallmark of the traditional Mediterranean diet, which has been associated with low incidence and prevalence of cancer, including colorectal cancer. The anticancer properties of olive oil have been attributed to its high levels of monounsaturated fatty acids, squalene, tocopherols, and phenolic compounds. Nevertheless, there is a growing interest in studying the role of olive oil phenolics in carcinogenesis. This review aims to provide an overview of the relationship between olive oil phenolics and colorectal cancer, in particular summarizing the epidemiologic, in vitro, cellular, and animal studies on antioxidant and anticarcinogenic effects of olive oil phenolics.�

�In the Mediterranean basin, olive oil, along with fruits, vegetables, and fish, is an important constituent of the diet, and is considered a major factor in preserving a healthy and relatively disease-free population. Epidemiological data show that the Mediterranean diet has significant protective effects against cancer and coronary heart disease. We present evidence that it is the unique profile of the phenolic fraction, along with high intakes of squalene and the monounsaturated fatty acid, oleic acid, which confer its health-promoting properties. The major phenolic compounds identified and quantified in olive oil belong to three different classes: simple phenols (hydroxytyrosol, tyrosol); secoiridoids (oleuropein, the aglycone of ligstroside, and their respective decarboxylated dialdehyde derivatives); and the lignans [(+)-1-acetoxypinoresinol and pinoresinol]. All three classes have potent antioxidant properties. High consumption of extra-virgin olive oils, which are particularly rich in these phenolic antioxidants (as well as squalene and oleic acid), should afford considerable protection against cancer (colon, breast, skin), coronary heart disease, and ageing by inhibiting oxidative stress.�

American Cancer Society, Work Study Group on Diet, Nutrition, and Cancer. American Cancer Society guidelines on diet, nutrition, and cancer. CA 41: 335-339 (1991).

European Atherosclerosis Society (EAS): Prevention of coronary heart disease: Scientific background and new clinical guidelines. Recommendations for the European Atherosclerosis Society prepared by the International Task Force for the Prevention of coronary heart disease. Nutr metab Cardiovasc Dis 2: 113-156 (1992)

National Institutes of Health: National Cholesterol Education Program. Second report of the expert panel on detection, evaluation, and treatment of high Blood Cholesterol in Adults (Adult Treatment Panel II). NIH Publication No.93-3095, 1995.